SS25 Induction Drugs (Etomidate & Ketamine) (Exam 2) Flashcards
(70 cards)
1
Q
In general, thiobarbiturates are much more _____ soluble and have a greater _______ than oxybarbiturates.
What atom do thiobarbiturates have in lieu of an oxygen in the second position (like oxybarbiturates)?
A
- Lipid; potency
- Sulfur
2
Q
A
- Goal: Surgical stimulation at peak time
- Study table
3
Q
What is unique about Etomidate’s organic chemical structure?
A
It is the only carboxylated imidazole containing compound.
4
Q
Etomidate:
- water-soluble vs lipid-soluble?
- Is it a weak acid or weak base?
A
- H₂O-soluble at acidic pH.
- Lipid-soluble at physiologic pH
- weak base
5
Q
What percentage of etomidate is propylene glycol? What is the result of this?
A
- 35% propylene glycol resulting in pain on injection.
6
Q
What additional route can Etomidate be given?
- Clinical significance?
A
- Sub-lingual
- Only drug with direct systemic absorption in oral mucosa that bypasses hepatic metabolism
- great for pediatrics
7
Q
Why does etomidate have a low incidence of myoclonus?
A
- Trick Question! Etomidate has a high incidence of myoclonus, just like all other induction agents.
8
Q
Etomidate MOA?
A
Indirect & Direct opening of Cl⎺ channels of GABA-a receptors → hyperpolarization
9
Q
Etomidate;
- Onset?
- Peak?
- Protein bound percent & which protein?
- E1/2?
A
- Onset: 1 minute
- Peak: 2 min
- 76% Albumin bound
- E1/2: 2- 5 hrs
10
Q
Etomidate:
- Vd
- Clearance? Compared to Thiopental?
- What is the result of this clearance?
A
- Large Vd (2.2 - 3.5 L/kg)
- CL: 10 - 20 mL/kg/min
- 5x faster than Thiopental = prompt awakening
- No hangover or accumulative drug efffect
11
Q
Etomidate:
- Metabolism?
- Elimination?
A
- Metabolism: Hydrolysis via CYP450 & plasma esterases
- Elimination: Urine 85% & Bile 10 - 13%
12
Q
What is the induction dosage range for etomidate?
A
- 0.3 mg/kg
13
Q
What is the best use for etomidate?
A
- Induction for unstable cardiac patients (patients with no cardiac reserve; low EF/ low LVEDP)
14
Q
What needs to be used concurrently with etomidate when performing a laryngoscopy? Why?
A
- Need Opioid, Etomidate has NO analgesic effects.
15
Q
What is Etomidate’s most common side effect?
- How often does this occur?
-Risk factors (3) per lecture?
A
- Involuntary Myoclonic Movements (Thalamocortical Tract)
- 50 - 80% of Etomidate administrations (highest of all the induction drugs)
- Seizure history, vaping, cannabis use
16
Q
What should be administered with etomidate to prevent involuntary myoclonic movements?
A
- Fentanyl 1-2 mcg/kg IV
- Opioids and benzos both help lessen occurence
17
Q
Etomidate has a dose dependent inhibition of the conversion of cholesterol to _________.
- What is this condition termed as?
- What does this mean clinically?
A
- Cortisol
- Adrenalcortical Suppression with prolonged use: inhibits stress = catecholamines depletion
- Prolonged mechanical ventilation, severe hypotension
- More common with continuous use vs. induction dose
18
Q
What can you give to pre-medicate if patient is increased risk for Adrenalcortical Suppression?
A
- Solumedrol or Prednisone
19
Q
How long does adrenocortical suppression with etomidate last?
- What two pathologies do you want to avoid the use of Etomidate in?
A
- 4 - 8 hrs
- Sepsis & hemorrhage (anything where you need an intact cortisol response)
20
Q
Compare Etomidate and Thiopental to plasma cortisol levels.
A
- Compared to Thiopental, Etomidate will lower plasma cortisol concentrations greatly.
21
Q
T/F: Etomidate is a direct cerebral vasoconstrictor.
A
- False!
- Etomidate is a Direct Cerebral Vasoconstrictor
22
Q
What effects does Etomidate have on CNS?
A
- Direct Cerebral Vasoconstrictor
- Decreases ↓CBF & ↓CMRO₂ by 35- 45%
- ↓ICP
(Prop and Thiopental does this as well)
23
Q
Etomidate:
- EEG compared to Thiopental?
- Can Etomidate induce seizures?
- Is SSEP amplitude increased or decreased affected? How does this effect the monitoring?
A
- Similar EEG to Thiopental but more frequent excitatory spikes
- May activate seizure foci
- Increases SSEP amplitude; can cause false positive imopulse (signal may not detect nerve is in danger of being cut during neuro sx)
24
Q
Etomidate CV effects:
A
- Most cardioprotective
- Minimal changes in HR, SV, SVR, CO, contractility,
- Decreased PAP
- Mild decrease in MAP
- No intra-arterial damage
(Remember: Thiopental causes Gangrene)
25
Though Etomidate is great for cardiac patients, what condition can result in significant hypotension if not treated prior to induction?
- **Hypovolemia**
- Esp. high dose induction (0.45 m/kg IV)
26
Histamine-induced hypotension via Etomidate is prevented by what med?
- Trick question! **Etomidate does NOT release histamine**.
27
Etomidate: Pulm effects
- **No change in minute ventilation**
- Transient increases RR q 3 - 5 mins offsets Vt decreases (compensatory)
- Less ventilation depression than barbiturates
- Rapid IV produces apnea
- Stimulates CO₂ medullary centers → **emerge breathing earlier** (avoids CO2 narcosis)
## Footnote
(Etomidate not as lipid soluble as barbs)
**(MV = Vt x RR)**
28
Ketamine:
- Derivative?
- What type of anesthesia does it produce?
- Phencyclidine derivative (PCP; "angel dust")
- Dissociative anesthesia
29
Ketamine:
- Primary receptor type?
- What 2 components of GA does Ketamine provide?
- NMDA receptor antagonist
-Amnestic and **intense analgesic** properties
30
Ketamine: dissociative anesthesia S&S
- Zonked state: "Eyes open but no one's home"
- Non-communicative but awake
- **Hypertonus** & purposeful skeletal muscle movements
- Cataleptic state (**slow nystagmic gaze**)
## Footnote
**Hypertonus = Risk for Rhabdo!**
-Also, maintain safety (restraints, etc.)
31
What are ketamine's 2 advantages over Propofol & Etomidate?
- **No pain at injection** (no propylene glycol)
- **Profound analgesia** at subanesthetic doses.
32
What are the 2 disadvantages of ketamine?
- Emergence delirium (Dissociation)
- Abuse potential (PCP)
33
What is Benzethonium Chloride? What is it's relevance?
- Ketamine preservative that adds to its effect
- **Inhibits ACh receptors**
34
Differentiate S (+) Ketamine, R (-) Ketamine, & Racemic mixtures,
- S (+) Ketamine (left-handed isomer)
1. More intense analgesia = **2x > Racemic; and 4x > R (-)**
2. ↑metabolism & recovery
3. Less salivation
4. ↓ incidence of emergence rxns
* Racemic
1. Inhibits Catecholamine uptake back into postganglionic sympathetic nerve endings (**cocaine-like effect**)
2. Less fatigue
3. Less cognitive impairment
## Footnote
R (-) Ketamine - R handed optical isomer
35
Ketamine: MOA?
- **Non-competitive inhibition** of **NMDA** (N-methyl-D-aspartate) receptors and **decreases pre-synaptic** release of **glutamate**
## Footnote
**Glutamate most abundant excitatory neurotransmitter in CNS**
- Glycine = obligatory co-agonist
36
Ketamine: Secondary receptor sites? (A lot)
- **Opioid (μ, δ, κ & weak σ)**
- Weak **GABA-a** -sedation effects
- **Muscaranic**: Anticholinergic properties = increase salivation, emergence delirium, bronchodilation, sympathomimetic)
- MOA: antinociceptive; may activate descending inhibitory pathway
- VG Na channels- local anesthetics effects
## Footnote
**Others: n-Ach, L-type Ca channels, MOA**
37
Ketamine:
- Onset?
- Peak? (IV & IM)
- Onset: Similar to Thiopental (rapid)
- Peak IV: 30 sec - 1 min
- Peak IM: 2 - 5 min (mostly for pediatric patients)
38
Ketamine: **Induction** DOAs
- Loss of consciousness (onset)
- ROC (return of consciousness)
- Full consciousness:
- Amnesia persists after ROC
- LOC (onset): **30 secs - 1 min**
- ROC: **10 - 20 mins**
- Full consciousness: **60 - 90 mins**
- Amnesia persists after ROC: **60 - 90 mins** (won't remember the drive home postop)
39
Ketamine:
- Protein bound percent?
- Lipid solubility?
- CL?
- What is the result of this?
- Vd?
- E1/2?
- PPB = Trick Question! **NOT plasma bound**
- Highly lipid soluble (**5-10x greater than thiopental**)
- CL: **high CL from brain**to tissues
- Vd = 3 L/kg (LARGE)
- E ½ = 2 - 3 hours
40
Ketamine:
- Clearance:
- Metabolism:
- Excretion:
- Clearance: **high** hepatic clearance (**1 L/min**)
- Metabolism: **CYP450**
- Excretion: Kidneys
41
What is the primary metabolite of ketamine?
- Significance?
- **Norketamine**: **active** metabolite (⅓-⅕ potency and **prolonged analgesia**
42
In what patient population is ketamine tolerance most often seen?
- **Burn** patients: Abuse & dependence potential
43
Ketamine Induction dose:
- IV
- IM
-PO
- IV: 0.5 - 1.5 mg/kg
- IM: 4 - 8 mg/kg
- PO: 10 mg/kg
44
Ketamine Maintenance dose: IV & IM
- IV: 0.2 - 0.5 mg/kg **for analgesia**
- IM: 4 - 8 mg/kg
## Footnote
IM dose same for Induction & Maintenance;
IV dose same as regular analgesic dose
45
Ketamine: Subanesthetic/ analgesic dose:
- IV: 0.2 - 0.5 mg/kg
46
Ketamine: Postop sedation & analgesia
- What type of sx is this dose used in?
- 1 - 2 mg/kg/**hr**
- **Pediatric cardiac sx**
47
Ketamine:
- Neuraxial epidural
- Spinal/ Intrathecal
- Epidural: 30 mg
-Spinal: 5 - 50 mg **in 3 cc of saline**
## Footnote
Intrathecal/spinal/subarachnoid
48
Ketamine is a potent sialagogue.
- Clinical significance?
- **Excessive secretions** during intubation
- Watch for **coughing/ laryngospasm**
49
What first line drug do you use to treat ketamine-induced salivary secretions?
- Dose?
- Other drugs options?
- First line: **Glycopyrrolate: 0.2 mg**
- Atropine, Scopaline (emergence delirium)
50
Ketamine: Clinical uses (8)
- Include rationale for each
- **Acutely hypovolemic** patients - stimulates SNS
- **Asthmatics & MH patients** - bronchodilator
- **Pediatric induction** - difficult to manage
- Cardiac sx - **CAD cocktail** - prevent iscemia
- **Burn & skin** dressings/ procedures
- **Reversal of opioid tolerance**
- **Psych** dx (OCD, PTSD, Depression)
- **Restless Leg** Syndriome (10mg/kg PO)
## Footnote
OTHER PEDI CHOICES: NASAL PRECEDEX, PO VERSED
51
Bonus: What volatiles and IV anesthetics induce bronchodilatory properties?
**SHIPMK**
- Sevo
- Halothane
- Isoflurane
- Propofol
- Midazolam
- Ketamine
52
- Why would we use a CAD cocktail?
- What's the ingredients?
- Help avoid cardiac event; synergisticaly reduces risk of dysrhythmias during sx
- Diazepam **0.5 mg/kg IV**
- Ketamine **0.5 mg/kg IV**
- Continuous Ketamine IV infusion: **15 - 30 mcg/kg/min**
53
When would you do an IM induction of a patient?
- What's the IM dose again?
- Uncooperative and difficult to manage patients; not just kids
- 4 - 8 mg/kg IM
54
When do we avoid Ketamine us?
- **Systemic/ Pulmonary HTN** - (increase up to 44%)
- **↑ICP** - Ketamine is potent cerebral vasodilator
55
Explain mechanism of Ketamine on ICP.
- **Potent cerebral vasodilator**
- **↑ICP** via **↑CBF** by 60%
- **↑CMRO₂** & **↑ glucose**
56
At what dose of Ketamine will the ICP **plateau**?
- 0.5 - 2mg/kg IV
## Footnote
Start low
57
Due to Ketamine's increased excitatory EEG activity, how much does seizure potential increase with administration?
- Trick question. **No increase in seizure potential with ketamine**
- Myoclonus may occur
## Footnote
Outlier: Etomidate alters sz threshold
58
Ketamine increases SSEP amplitude. This may be reduced by _________ gas use.
- Nitrous
59
Ketamine: CV effects
How can CV effects be blunted?
- SNS stimulation ( **↑ in SBP, PAP, HR, CO, CMRO₂,**)
- **↑Epi & NE**
- Blunted via pre-med with **benzo's, inhaled anesthetics, or nitrous gas**
60
You just gave Ketamine and you patient's BP and CO dropped significantly (marked hypotension).
- What happened?
- How do you treat it?
- Most sympathetic drug
- **Depleted catecholamine stores**
- **Give Epi** - direct acting, non-selective
- **direct myocardial depressant**
- No histamine release
## Footnote
**Etomidate: most CV stable**
61
Ketamine: Pulm effects
- **No depression of ventilation with CO₂ response maintained**.
- ↑ salivary excretions
- **Intact upper airway tone & reflexes**.
- **Bronchodilator + no histamine release**.
## Footnote
Good for pulm patient, with healthy heart
62
Ketamine-induced emergence delirium S&S:
- Psychedelic effects (5-30% of patients)
- Visual, auditory, proprioceptive illusions
- **Morbid & vivid dreams in color/hallucinations up to 24 hours**
- Not an adverse reaction
63
Ketamine-induced emergence delirium MOA:
- **Depression of inferior colliculus & medial geniculate nucleus**
64
Ketamine-induced emergence delirium **prevention**
- **IV benzo** 5 mins prior
- **Clonidine or Precedex**
65
Ketamine other systems effects :
- Inhibit cytosolic free [Ca] = **Enhances non-depolarizing NMBAs** (ie: Rocuronium)
- **Inhibit plasma cholisterases** = **Prolong apnea from Succinylcholine**
- PLT aggregation inhibition (low significane)
66
Ketamine: Most common drug interactions
- Volatiles (**Iso, Sevo, Des**) → hypotension
- **Non-depolarizing** NMBAs → enhanced
- **Succ**inylcholine → prolonged
67
What are the risks and benefits of Ketamine use in OSA?
- Benefits: Preservation of Upper airway reflexes (**on subanesthetic doses**) & Ventilatory function
- Risks: Psych effects, SNS activation, hypersalivation
## Footnote
Bronchodilator
68
Which induction agent has the highest analgesic properties?
- Ketamine
69
Ketafol
- Ketafol = Propofol & Ketamine mixture
- Not approved FDA but facility trumps FDA
- **Propofol is NOT chiral = unstable **
- Not recommended to mix Prop with any drug
- Prop + Lido (lipid bubbles = PE)
- Prop + Succ (BBW peds) - some facilities approved; Pre-treat Glycopyrolate
70
Sterile Prep USP 797
- Sterile compounding
-Immediate use rule: Single dose meds
- **Able to draw up within 4 hrs pre-op** (new)
- PPE
- Aseptic
